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通过多价疏水性调节 DNA/脂质界面。

Modulating the DNA/Lipid Interface through Multivalent Hydrophobicity.

机构信息

Programmable Biomaterials Laboratory, Institute of Materials, School of Engineering, Ecole Polytechnique Fédérale Lausanne, Lausanne 1015, Switzerland.

Interfaculty Bioengineering Institute, School of Engineering, Ecole Polytechnique Fédérale Lausanne, Lausanne 1015, Switzerland.

出版信息

Nano Lett. 2024 Sep 11;24(36):11210-11216. doi: 10.1021/acs.nanolett.4c02564. Epub 2024 Jul 26.

DOI:10.1021/acs.nanolett.4c02564
PMID:39054892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11403765/
Abstract

Lipids and nucleic acids are two of the most abundant components of our cells, and both molecules are widely used as engineering materials for nanoparticles. Here, we present a systematic study of how hydrophobic modifications can be employed to modulate the DNA/lipid interface. Using a series of DNA anchors with increasing hydrophobicity, we quantified the capacity to immobilize double-stranded (ds) DNA to lipid membranes in the liquid phase. Contrary to electrostatic effects, hydrophobic anchors are shown to be phase-independent if sufficiently hydrophobic. For weak anchors, the overall hydrophobicity can be enhanced following the concept of multivalency. Finally, we demonstrate that structural flexibility and anchor orientation overrule the effect of multivalency, emphasizing the need for careful scaffold design if strong interfaces are desired. Together, our findings guide the design of tailored DNA/membrane interfaces, laying the groundwork for advancements in biomaterials, drug delivery vehicles, and synthetic membrane mimics for biomedical research and nanomedicine.

摘要

脂质和核酸是我们细胞中最丰富的两种成分,这两种分子都被广泛用作纳米粒子的工程材料。在这里,我们系统地研究了如何利用疏水性修饰来调节 DNA/脂质界面。我们使用一系列疏水性逐渐增加的 DNA 接头,定量研究了在液相中将双链 DNA(dsDNA)固定到脂质膜上的能力。与静电效应相反,如果疏水性足够强,疏水性接头是与相无关的。对于弱接头,可以根据多价结合的概念增强整体疏水性。最后,我们证明了结构的灵活性和接头的方向会超过多价结合的影响,这强调了如果需要强界面,就需要仔细设计支架。总的来说,我们的发现为定制 DNA/膜界面的设计提供了指导,为生物材料、药物输送载体以及用于生物医学研究和纳米医学的合成膜模拟物的发展奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/2bae95c94715/nl4c02564_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/4bb222205ef0/nl4c02564_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/d4ce49ddaf52/nl4c02564_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/6ae253af51e0/nl4c02564_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/2bae95c94715/nl4c02564_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/4bb222205ef0/nl4c02564_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/d4ce49ddaf52/nl4c02564_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/6ae253af51e0/nl4c02564_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05c/11403765/2bae95c94715/nl4c02564_0004.jpg

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本文引用的文献

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Stabilizing Polymer Coatings Alter the Protein Corona of DNA Origami and Can Be Engineered to Bias the Cellular Uptake.稳定聚合物涂层改变了DNA折纸术的蛋白质冠层,并且可以通过工程设计来偏向细胞摄取。
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正在研发中的基因和亚单位疫苗的基于脂质的传递系统。
Mol Biotechnol. 2023 May;65(5):669-698. doi: 10.1007/s12033-022-00624-8. Epub 2022 Dec 3.
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Multivalent Pattern Recognition through Control of Nano-Spacing in Low-Valency Super-Selective Materials.通过控制低价超选择性材料中的纳米间距实现多价模式识别。
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Nano Lett. 2022 Mar 23;22(6):2506-2513. doi: 10.1021/acs.nanolett.2c00275. Epub 2022 Mar 10.
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Design and Preparation of Solid Lipid Nanoparticle (SLN)-Mediated DNA Vaccines.固体脂质纳米粒(SLN)介导的 DNA 疫苗的设计与制备。
Methods Mol Biol. 2022;2412:355-366. doi: 10.1007/978-1-0716-1892-9_18.
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Hydrophobic Interactions between DNA Duplexes and Synthetic and Biological Membranes.DNA 双链体与合成和生物膜之间的疏水相互作用。
J Am Chem Soc. 2021 Jun 9;143(22):8305-8313. doi: 10.1021/jacs.0c13235. Epub 2021 May 20.
8
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Nucleic Acids Res. 2021 Jul 2;49(W1):W491-W498. doi: 10.1093/nar/gkab324.
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Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures.阳离子调控 DNA 纳米结构的膜附着和功能。
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